Covalent organic frameworks (COFs) are a novel class of organic porous materials that, in recent years, have gained much attention for their applications as nanocarriers toward nanomedicine development. Inspired by this, we introduce for the first time a novel theranostic nanoplatform that combines iodine ligand 5-amino-2,4,6-triiodoisophthalic acid (ATIPA)-decorated porphyrin-based covalent organic frameworks (pCOF-I) designed for effective photodynamic therapy (PDT), doxorubicin (DOX) encapsulation, and computed tomography (CT) imaging toward melanoma treatment. In the design of this COF, we have successfully integrated the iodine ligand with porphyrin. The synthesized mesoporous nanoplatform was loaded with DOX and further modified by COOH-PEG-NH2, which was conjugated with the AS1411 aptamer to be targeted to B16F0 melanoma cells. Comprehensive characterizations verified the successful synthesis and controlled release of DOX from the synthesized COF. In vitro evaluation against B16F0 showed combined chemo-PDT therapy. In addition, higher cellular uptake and toxicity were observed for the targeted platform compared to the non-targeted one towards B16F0. The porphyrin molecules imparted to the pCOF-I nanoparticles (NPs) a significant capacity for light induced reactive oxygen species (ROS) generation, demonstrating remarkable PDT efficacy in both in vivo and in vitro environments. An in vivo investigation on B16F0 ectopic tumor model of melanoma in mice confirmed the potential for showed combined chemo-PDT therapy chemo-PDT in preclinical stage while approving guided delivery and tumor accumulation of AS1411 aptamer-tagged systems. On the other hand, the prepared platform demonstrated desirable CT-scan imaging of B16F0 tumorized mice 6 and 24 h post-injection. Notably, this is the first report of an AS1411 aptamer-targeted pCOF-I system for CT imaging-guided combined chemo-PDT, marking a significant step forward in multimodal cancer treatment strategies.

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